FDA approves Keytruda + Herceptin in HER2-positive gastric or gastroesophageal junction adenocarcinoma – Merck Inc.

Merck Inc announced that the FDA has approved Keytruda (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with Herceptin (trastuzumab), fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. This indication is approved under accelerated approval based on tumor response rate and durability of response; continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials

This approval is based on data from the ongoing Phase III KEYNOTE-811 trial, in which Keytruda in combination with trastuzumab and either 5-fluorouracil plus cisplatin or capecitabine plus oxaliplatin demonstrated a statistically significant objective response rate (ORR) of 74% (95% CI, 66-82) for patients who received the regimen with Keytruda versus 52% (95% CI, 43-61) for those who received trastuzumab and chemotherapy alone (p<0.0001). For patients who received the regimen with Keytruda, the complete response rate was 11% and the partial response rate was 63%. For patients who received trastuzumab and chemotherapy alone, the complete response rate was 3.1% and the partial response rate was 49%.

KEYNOTE-811 was a multicenter, randomized, double-blind, placebo-controlled trial that was designed to enroll 692 patients with HER2-positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for metastatic disease. At the time of the interim analysis, ORR and DOR were assessed in the first 264 patients randomized. Among the 264 patients, the population characteristics were: median age of 62 years (range, 19 to 84), 41% age 65 or older; 82% male; 63% white, 31% Asian and 0.8% Black; 47% Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, and 53% ECOG PS of 1. Ninety-seven percent of patients had metastatic disease (stage IV), and 3% had locally advanced un-resectable disease. Eighty-seven percent had tumors that expressed PD-L1 with a CPS at least 1. Ninety-one percent (n=240) had tumors that were not microsatellite instability-high (MSI-H), 1% (n=2) had tumors that were MSI-H, and in 8% (n=22), the status was not known. Eighty-seven percent of patients received CAPOX (capecitabine + oxaliplatin).

A statistically significant improvement in ORR was demonstrated in patients randomized to Keytruda in combination with trastuzumab and chemotherapy compared with placebo in combination with trastuzumab and chemotherapy. The safety analysis of the study included 217 patients with HER2-positive gastric cancer who received Keytruda 200 mg, trastuzumab, and CAPOX (n=189) or FP (n=28) every three weeks, compared to 216 patients who received placebo, trastuzumab, and CAPOX (n=187) or FP (n=29) every three weeks. The median duration of exposure to Keytruda was 5.8 months (range, 1 day to 17.7 months). Keytruda and placebo were discontinued due to adverse reactions in 6% of patients in each arm. The most common adverse reaction resulting in permanent discontinuation of Keytruda was pneumonitis (1.4%). Adverse reactions leading to interruption of Keytruda occurred in 58% of patients.